scholarly journals Evidence for vesicle-mediated antigen export by the human pathogen Babesia microti

2019 ◽  
Vol 2 (3) ◽  
pp. e201900382 ◽  
Author(s):  
Jose Thekkiniath ◽  
Nicole Kilian ◽  
Lauren Lawres ◽  
Meital A Gewirtz ◽  
Morven M Graham ◽  
...  

The apicomplexan parasite Babesia microti is the primary agent of human babesiosis, a malaria-like illness and potentially fatal tick-borne disease. Unlike its close relatives, the agents of human malaria, B. microti develops within human and mouse red blood cells in the absence of a parasitophorous vacuole, and its secreted antigens lack trafficking motifs found in malarial secreted antigens. Here, we show that after invasion of erythrocytes, B. microti undergoes a major morphogenic change during which it produces an interlacement of vesicles (IOV); the IOV system extends from the plasma membrane of the parasite into the cytoplasm of the host erythrocyte. We developed antibodies against two immunodominant antigens of the parasite and used them in cell fractionation studies and fluorescence and immunoelectron microscopy analyses to monitor the mode of secretion of B. microti antigens. These analyses demonstrate that the IOV system serves as a major export mechanism for important antigens of B. microti and represents a novel mechanism for delivery of parasite effectors into the host by this apicomplexan parasite.

2000 ◽  
Vol 68 (5) ◽  
pp. 2783-2790 ◽  
Author(s):  
Michael J. Lodes ◽  
Raymond L. Houghton ◽  
Elizabeth S. Bruinsma ◽  
Raodoh Mohamath ◽  
Lisa D. Reynolds ◽  
...  

ABSTRACT Increased recognition of the prevalence of human babesiosis in the United States, together with rising concern about the potential for transmission of this infection by blood transfusion, has provided motivation to develop definitive serologic and molecular tests for the causative agent, Babesia microti. To develop more sensitive and specific assays for B. microti, we screened a genomic expression library with patient serum pools. This screening resulted in the identification of three classes of novel genes and an additional two novel, unrelated genes, which together encode a total of 17 uniqueB. microti antigens. The first class (BMN1-2 family) of genes encodes seven closely related antigens with a degenerate six-amino-acid repeat that shows limited homology toPlasmodium sp. merozoite and sporozoite surface antigens. A second class (BMN1-8 family) of genes encodes six related antigens, and the third class (BMN1-17 family) of genes encodes two related antigens. The two remaining genes code for novel and unrelated sequences. Among the three classes of antigens and remaining novel sequences, five were chosen to code for the most immunodominant antigens (BMN1-2, -9, -15, and -17 and MN-10). Western blot analysis with the resulting recombinant proteins indicated that these antigens were targets of humoral immune responses during B. microti infection in humans.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen L. Knapp ◽  
Nancy A. Rice

Borrelia burgdorferi, the causative agent of Lyme disease, andBabesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern United States. These pathogens are transmitted via the bite of an infected tick vector,Ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously. Clinical presentation of the diseases is heterogeneous and ranges from mild flu-like symptoms to near-fatal cardiac arrhythmias. While the reason for the variability is not known, the possibility exists that concomitant infection with bothB. burgdorferiandB. microtimay synergistically increase disease severity. In an effort to clarify the current state of understanding regarding coinfection withB. burgdorferiandB. microti, in this review, we discuss the geographical distribution and pathogenesis of Lyme disease and babesiosis in the United States, the immunological response of humans toB. burgdorferiorB. microtiinfection, the existing knowledge regarding coinfection disease pathology, and critical factors that have led to ambiguity in the literature regarding coinfection, in order to eliminate confusion in future experimental design and investigation.


Parasitology ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 691-699 ◽  
Author(s):  
A. SAITO-ITO ◽  
N. TAKADA ◽  
F. ISHIGURO ◽  
H. FUJITA ◽  
Y. YANO ◽  
...  

SUMMARYField rodent surveys forBabesiainfection were performed from 2002 to 2005 in the vicinities of human babesiosis occurrences in Taiwan and mainland China.Babesia microtiwas identified by microscopical examination and/or PCR in 1Rattus coxingaand 1Crocidura horsfieldiiin central Taiwan and in 13Niviventer confucianusand 1Apodemus agrariusin Zhejiang and Fujian Provinces of southeastern China. Of 15B. microtisamples detected by PCR, all except 1 were shown to be the Kobe-type, the aetiological small subunit rRNA gene-type of the first Japanese patient; the exception was also a Kobe-related type. The Kobe-type had been found in rodents only in a few places including the human infection occurrence place in Japan. The internal transcribed spacer 1 to 2 sequences of the Taiwanese and Chinese Kobe-types were very similar to each other but considerably different (approx. 94% pairwise identities) from that of the Japanese Kobe-type. A Taiwanese Kobe-type strain was serologically differentiated from the Kobe strain originating from the Japanese first patient. The distribution of the Kobe-type in the vicinities of human babesiosis occurrences in Taiwan and China as well as in Japan is suggestive of involvement of the Kobe-type in Asian human babesiosis.


Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1447
Author(s):  
Abhinav Kumar ◽  
Jane O'Bryan ◽  
Peter J. Krause

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (Ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease.


Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1563
Author(s):  
Scott Meredith ◽  
Miranda Oakley ◽  
Sanjai Kumar

The biology of intraerythrocytic Babesia parasites presents unique challenges for the diagnosis of human babesiosis. Antibody-based assays are highly sensitive but fail to detect early stage Babesia infections prior to seroconversion (window period) and cannot distinguish between an active infection and a previously resolved infection. On the other hand, nucleic acid-based tests (NAT) may lack the sensitivity to detect window cases when parasite burden is below detection limits and asymptomatic low-grade infections. Recent technological advances have improved the sensitivity, specificity and high throughput of NAT and the antibody-based detection of Babesia. Some of these advances include genomics approaches for the identification of novel high-copy-number targets for NAT and immunodominant antigens for superior antigen and antibody-based assays for Babesia. Future advances would also rely on next generation sequencing and CRISPR technology to improve Babesia detection. This review article will discuss the historical perspective and current status of technologies for the detection of Babesia microti, the most common Babesia species causing human babesiosis in the United States, and their implications for early diagnosis of acute babesiosis, blood safety and surveillance studies to monitor areas of expansion and emergence and spread of Babesia species and their genetic variants in the United States and globally.


Healthcare ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 155 ◽  
Author(s):  
John D. Scott ◽  
Kerry L. Clark ◽  
Nikki M. Coble ◽  
Taylor R. Ballantyne

Lyme disease and human babesiosis are the most common tick-borne zoonoses in the Temperate Zone of North America. The number of infected patients has continued to rise globally, and these zoonoses pose a major healthcare threat. This tick-host-pathogen study was conducted to test for infectious microbes associated with Lyme disease and human babesiosis in Canada. Using the flagellin (flaB) gene, three members of the Borrelia burgdorferi sensu lato (Bbsl) complex were detected, namely a Borrelia lanei-like spirochete, Borrelia burgdorferi sensu stricto (Bbss), and a distinct strain that may represent a separate Bbsl genospecies. This novel Bbsl strain was detected in a mouse tick, Ixodes muris, collected from a House Wren, Troglodytes aedon, in Quebec during the southward fall migration. The presence of Bbsl in bird-feeding larvae of I. muris suggests reservoir competency in three passerines (i.e., Common Yellowthroat, House Wren, Magnolia Warbler). Based on the 18S ribosomal RNA (rRNA) gene, three Babesia species (i.e., Babesia divergens-like, Babesia microti, Babesia odocoilei) were detected in field-collected ticks. Not only was B. odocoilei found in songbird-derived ticks, this piroplasm was apparent in adult questing blacklegged ticks, Ixodes scapularis, in southern Canada. By allowing live, engorged ticks to molt, we confirm the transstadial passage of Bbsl in I. muris and B. odocoilei in I. scapularis. Bbss and Babesia microti were detected concurrently in a groundhog tick, Ixodes cookei, in Western Ontario. In Alberta, a winter tick, Dermacentor albipictus, which was collected from a moose, Alces alces, tested positive for Bbss. Notably, a B. divergens-like piroplasm was detected in a rabbit tick, Haemaphysalis leporispalustris, collected from an eastern cottontail in southern Manitoba; this Babesia species is a first-time discovery in Canada. This rabbit tick was also co-infected with Borrelia lanei-like spirochetes, which constitutes a first in Canada. Overall, five ticks were concurrently infected with Babesia and Bbsl pathogens and, after the molt, could potentially co-infect humans. Notably, we provide the first authentic report of I. scapularis ticks co-infected with Bbsl and B. odocoilei in Canada. The full extent of infectious microorganisms transmitted to humans by ticks is not fully elucidated, and clinicians need to be aware of the complexity of these tick-transmitted enzootic agents on human health. Diagnosis and treatment must be administered by those with accredited medical training in tick-borne zoonosis.


2003 ◽  
Vol 65 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Satoru ARAI ◽  
Masayoshi TSUJI ◽  
Ikuo KAIHO ◽  
Haruka MURAYAMA ◽  
Aya ZAMOTO ◽  
...  

2014 ◽  
Vol 7 (1) ◽  
Author(s):  
Xia Zhou ◽  
Shang Xia ◽  
Ji-Lei Huang ◽  
Ernest Tambo ◽  
Hong-Xiang Zhuge ◽  
...  

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